STAT3 Activates the Pentraxin 3 Gene in Chronic Lymphocytic Leukemia Cells.

Pentraxin-related protein 3 (PTX3), commonly produced by myeloid and endothelial cells, is a humoral pattern recognition protein of the innate immune system. Because PTX3 plasma levels of patients with chronic lymphocytic leukemia (CLL) are high and most circulating cells in patients with CLL are CLL cells, we reasoned that CLL cells produce PTX3. Western immunoblotting revealed that low-density cells from seven of seven patients with CLL produce high levels of PTX3, flow cytometry analysis revealed that the PTX3-producing cells are B lymphocytes coexpressing CD19 and CD5, and confocal microscopy showed that PTX3 is present in the cytoplasm of CLL cells. Because STAT3 is constitutively activated in CLL cells, and because we identified putative STAT3 binding sites within the PTX3 gene promoter, we postulated that phosphorylated STAT3 triggers transcriptional activation of PTX3. Immunoprecipitation analysis of CLL cells' chromatin fragments showed that STAT3 Abs precipitated PTX3 DNA. STAT3 knockdown induced a marked reduction in PTX3 expression, indicating a STAT3-induced transcriptional activation of the PTX3 gene in CLL cells. Using an EMSA, we established and used a dual-reporter luciferase assay to confirm that STAT3 binds the PTX3 gene promoter. Downregulation of PTX3 enhanced apoptosis of CLL cells, suggesting that inhibition of PTX3 might benefit patients with CLL.

STAT3 induces the expression of GLI1 in chronic lymphocytic leukemia cells.

The glioma associated oncogene-1 (GLI1), a downstream effector of the embryonic Hedgehog pathway, was detected in chronic lymphocytic leukemia (CLL), but not normal adult cells. GLI1 activating mutations were identified in 10% of patients with CLL. However, what induces GLI1 expression in GLI1-unmutated CLL cells is unknown. Because signal transducer and activator of transcription 3 (STAT3) is constitutively activated in CLL cells and sequence analysis detected putative STAT3-binding sites in the GLI1 gene promoter, we hypothesized that STAT3 induces the expression of GLI1. Western immunoblotting detected GLI1 in CLL cells from 7 of 7 patients, flow cytometry analysis confirmed that CD19+/CD5+ CLL cells co-express GLI1 and confocal microscopy showed co-localization of GLI1 and phosphorylated STAT3. Chromatin immunoprecipitation showed that STAT3 protein co-immunoprecipitated GLI1 as well as other STAT3-regulated genes. Transfection of CLL cells with STAT3-shRNA induced a mark decrease in GLI1 levels, suggesting that STAT3 binds to and induces the expression of GLI1 in CLL cells. An electromobility shift assay confirmed that STAT3 binds, and a luciferase assay showed that STAT3 activates the GLI1 gene. Transfection with GLI1-siRNA significantly increased the spontaneous apoptosis rate of CLL cells, suggesting that GLI1 inhibitors might provide therapeutic benefit to patients with CLL.

The costs of mindfulness at work: The moderating role of mindfulness in surface acting, self-control depletion, and performance outcomes.

By and large, research in organizational behavior and psychology has emphasized that mindfulness should have positive implications for employee well-being and performance, largely through benefits to self-control. Although some have noted that mindfulness could also have a "dark side," researchers have yet to examine the potential costs of being mindful at work. Building on prior studies that have found that mindfulness leads to lower levels of surface acting, we investigate the possibility that when mindful employees engage in surface acting, it may contribute to greater self-control depletion, which in turn, results in undesirable performance outcomes. Using six field studies, we collected data at multiple points in time from both employees and their supervisors to test our theoretical model. In two Study 1 samples, we found that mindfulness moderated the relationship between surface acting and self-control depletion, such that this relationship was stronger for more mindful individuals. In four Study 2 samples, we replicated our Study 1 results and found that the mediated relationship between surface acting and five dimensions of employee performance via self-control depletion is moderated by mindfulness at the first stage, such that this mediated relationship is stronger for more mindful individuals. We discuss the implications of this work for future investigations of mindfulness, self-control, emotional labor, and performance outcomes. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Synthesis and biological evaluation of a novel photo-activated histone deacetylase inhibitor.

Hydroxamic acid-based histone deacetylase inhibitors (HDACi) are a class of epigenetic agents with potentially broad therapeutic application to several disease states including post angioplasty mediated neointimal hyperplasia (NIH). Precise spatiotemporal control over the release of HDACi at the target blood vessel site is required for the safe and successful therapeutic use of HDACi in the setting of drug eluting balloon catheter (DEBc) angioplasty treatment of NIH. We aimed to develop and characterise a novel photoactive HDACi, as a potential coating agent for DEBc. Metacept-3 1 was caged with a photo-labile protecting group (PPG) to synthesise a novel UV365nm active HDACi, caged metacept-3 15. Conversion of caged metacept-3 15 to active/native metacept-3 1 by UV365nm was achievable in significant quantities and at UV365nm power levels in the milliwatt (mW) range. In vitro evaluation of the biological activity of pre and post UV365nm activation of caged metacept-3 15 identified significant HDACi activity in samples exposed to short duration, mW range UV365nm. Toxicity studies performed in human umbilical vein endothelial cells (HUVEC's) identified significantly reduced toxicity of caged metacept-3 15 pre UV365nm exposure compared with native metacept-3 1 and paclitaxel (PTX). Taken together these findings identify a novel photo-activated HDACi, caged metacept-3 15, with pharmacokinetic activation characteristics and biological properties which may make it suitable for evaluation as a novel coating for targeted DEBc angioplasty interventions.

No obligation? How gender influences the relationship between perceived organizational support and organizational citizenship behavior.

Previous research indicates that perceived organizational support (POS) elicits felt obligation on the part of employees who, in turn, reciprocate by helping the organization through the performance of organizational citizenship behavior (OCB). However, because gender roles dictate that women should be more helpful than men, women may feel more obligated to engage in OCB even when they experience relatively low levels of POS, whereas men may perform OCB only when they experience relatively high levels of POS. In this article, we use social role theory to predict that the relationship between POS and 3 types of OCB will be stronger for men than for women. Our results, using 4 samples of employee-supervisor dyads, support this prediction. Further, in 2 of those samples, we also investigate the possibility that gender moderates the positive POS-felt obligation relationship and the indirect effect of POS on OCB via felt obligation. Taken together, we find evidence of first-stage moderated-mediation. Specifically, the relationship between POS and felt obligation is moderated by gender, such that this relationship is stronger for men than for women (who feel more obligation, even at relatively low levels of POS). Felt obligation mediated the POS-OCB relationship, but only for men. Our findings suggest that men are more likely than women to need POS to feel obligated to make reciprocal organizational exchanges. Implications and future research directions are discussed. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Decreasing formalin concentration improves quality of DNA extracted from formalin-fixed paraffin-embedded tissue specimens without compromising tissue morphology or immunohistochemical staining.

Genomic technologies are increasingly used clinically for both diagnosis and guiding cancer therapy. However, formalin fixation can compromise DNA quality. This study aimed to optimise tissue fixation using normal colon, liver and uterus (n=8 each) by varying neutral buffered formalin (NBF) concentration (1%-5% w/v) and fixation time (24-48 hours). Fixation using 4% NBF improved DNA quality (assessed by qPCR) compared with routine (4% unbuffered formal saline-fixed) specimens (p<0.01). Further improvements were achieved by reducing NBF concentration (p<0.00001), whereas fixation time had no effect (p=0.110). No adverse effects were detected by histopathological or QuPath morphometric analysis. Immunohistochemistry for multicytokeratin and α-smooth muscle actin revealed no changes in staining specificity or intensity in any tissue other than on liver multicytokeratin staining intensity, where the effect of fixation time was more significant (p=0.0004) than NBF concentration (p=0.048). Thus, reducing NBF concentration can maximise DNA quality without compromising tissue morphology or standard histopathological analyses.

STAT3-Induced Wnt5a Provides Chronic Lymphocytic Leukemia Cells with Survival Advantage.

The wingless and integration site growth factor-5a (Wnt5a) is a ligand of the receptor tyrosine kinase-like orphan receptor-1 (ROR1). Because both Wnt5a and ROR1 are expressed in circulating chronic lymphocytic leukemia (CLL) cells, and because in other cell types, STAT3, which is constitutively activated in CLL, induces Wnt5a signaling, we wondered whether STAT3 induces the expression of Wnt5a in CLL cells. Sequence analysis detected four putative STAT3 binding sites in close proximity to the Wnt5a gene promoter's start codon. Chromatin immunoprecipitation and EMSA revealed that STAT3 binds to the Wnt5a gene promoter, and a luciferase assay showed that STAT3 activates the Wnt5a gene. Additionally, transfection of peripheral blood CLL cells with STAT3 short hairpin RNA downregulated Wnt5a mRNA and protein levels, suggesting that STAT3 binds to the Wnt5a gene promoter and induces the expression of Wnt5a in CLL cells. Flow cytometry and confocal microscopy determined that both Wnt5a and its receptor ROR1 are coexpressed on the surface of CLL cells, and Western immunoblotting showed an inverse correlation between Wnt5a and ROR1 protein levels, implying that, regardless of CLL cells' ROR1 levels, blocking the interaction between Wnt5a and ROR1 might be beneficial to patients with CLL. Indeed, transfection of CLL cells with Wnt5a small interfering RNA reduced Wnt5a mRNA and protein levels and significantly increased the spontaneous apoptotic rate of CLL cells. Taken together, our data unravel an autonomous STAT3-driven prosurvival circuit that provides circulating CLL cells with a microenvironment-independent survival advantage.

STAT3 is constitutively acetylated on lysine 685 residues in chronic lymphocytic leukemia cells.

Signal transducer and activator of transcription (STAT)-3 might be phosphorylated or acetylated. Unlike the phosphorylation of STAT3, little is known about the acetylation of STAT3 in chronic lymphocytic leukemia (CLL) cells. Because acetylation activates STAT3 transcription, we sought to study the acetylation status of STAT3 in CLL cells. Using Western immunoblotting, immunoprecipitation, and flow cytometry we found that, apart from its constitutive serine phosphorylation, STAT3 is constitutively acetylated on lysine 685 residues. Because the acetyltransferase p300 was found to acetylate STAT3 on lysine 685 residues, we wondered whether p300 acetylates STAT3 in CLL cells. Using Western immunoblotting we detected high levels of p300 protein in CLL but not normal B cells. Transfection of CLL cells with p300 small-interfering (si) RNA downregulated p300 transcripts as well as p300 and acetyl-STAT3 protein levels. In addition, p300 siRNA attenuated STAT3-DNA binding and downregulated mRNA levels of STAT3-regulated genes. Furthermore, transfection of CLL cells with p300-siRNA induced a 3-fold increase in the rate of spontaneous apoptosis. Taken together, our data suggest that in CLL cells STAT3 p300 induces constitutive acetylation and activation of STAT3. Whether inhibition of STAT3 acetylation might provide clinical benefit in patients with CLL remains to be determined.

STAT3-activated CD36 facilitates fatty acid uptake in chronic lymphocytic leukemia cells.

Although several studies established that unlike normal B cells chronic lymphocytic leukemia (CLL) cells metabolize fatty acids (FA), how CLL cells internalize FA is poorly understood. Because in various cell types CD36 facilitates FA uptake, we wondered whether a similar mechanism is operative CLL. We found that CD36 levels are higher in CLL cells than in normal B cells, and that small interfering RNA, CD36 neutralizing antibodies or sulfosuccinimidyl oleate (SSO) that inhibits CD36 significantly reduced the oxygen consumption of CLL cells incubated with FA. Because CD36 is oeverexpressed and STAT3 is constitutively activated in CLL cells, we wondered whether STAT3 induces CD36 expression. Sequence analysis identified putative STAT3 binding sites in the CD36 gene promoter. Chromatin immunoprecipitation and an electrophoretic mobility shift assay revealed that STAT3 binds to the CD36 gene promoter. A luciferase assay and STAT3-small hairpin RNA, that significantly decreased the levels of CD36 in CLL cells, established that STAT3 activates the transcription of the CD36 gene. Furthermore, SSO induced a dose-dependent apoptosis of CLL cells. Taken together, our data suggest that STAT3 activates CD36 and that CD36 facilitates FA uptake in CLL cells. Whether CD36 inhibition would provide clinical benefits in CLL remains to be determined.

Negative beliefs about accepting coworker help: Implications for employee attitudes, job performance, and reputation.

For more than 30 years, researchers have investigated interpersonal helping in organizations, with much of this work focusing on understanding why employees help their colleagues. Although this is important, it is also critical that employees are willing to accept assistance that is offered by peers. Indeed, helping behavior should only enhance individual and organizational effectiveness if employees are actually willing to accept offers of assistance. Unfortunately, employees may sometimes have reservations about accepting help from their peers. In four studies, we examine the negative beliefs that employees have about accepting help from coworkers. In Study 1, we use inductive research to qualitatively understand why employees accept or decline coworker help. In Study 2, we develop a preliminary, second-order reflective measure of negative beliefs about accepting coworker help that is indicated by the five specific (first-order) reservations about accepting help identified in Study 1-diminished image, reciprocity obligation, self-reliance, coworker mistrust, and coworker incompetence. In Study 3, we refine our scale and demonstrate its convergent, discriminant, and criterion-related validity. Finally, in Study 4, we investigate the consequences of negative beliefs about accepting coworker help. We find that those who hold more negative beliefs are less likely to receive help from peers (and supervisors), report more negative job attitudes, and have lower levels of in-role performance, citizenship behavior, and creativity. Furthermore, employees with more negative beliefs about accepting help from coworkers are seen less favorably by their supervisors. Implications and future research directions are discussed. (PsycINFO Database Record

Ibrutinib inhibits free fatty acid metabolism in chronic lymphocytic leukemia.

Unlike normal B-cells, and similar to fat cells, chronic lymphocytic leukemia (CLL) cells aberrantly express lipoprotein lipase (LPL), which contributes to free fatty acids (FFAs) metabolism. Here we show that, in CLL cells, the B-cell receptor (BCR) inhibitor ibrutinib reduced LPL mRNA and protein levels and inhibited FFA metabolism in vitro. Likewise, in CLL cells from ibrutinib-treated patients, FFA metabolism was reduced and eventually stopped. Because ibrutinib disrupts CLL cells' ability to use FFAs for energy production, and because various BCR-dependent cellular functions rely on a continuous supply of chemical energy, ibrutinib interrupts several pathways imperative for cellular function in CLL cells.

Ruxolitinib for symptom control in patients with chronic lymphocytic leukaemia: a single-group, phase 2 trial.

BACKGROUND: Disease-related symptoms impair the quality of life of patients with chronic lymphocytic leukaemia (CLL) who do not require systemic therapy. Available therapies are not specifically aimed at symptom control. Because stimulation of the B-cell receptor activates JAK2 in CLL cells and the JAK2 inhibitor ruxolitinib improves symptoms in patients with myelofibrosis, we postulated that ruxolitinib would improve disease-related symptoms in patients with CLL. We did a phase 2 trial of ruxolitinib to test this hypothesis. METHODS: Symptomatic patients with CLL who did not require systemic therapy were enrolled at MD Anderson Cancer Center (Houston, TX, USA) between Sept 15, 2014, and Sept 20, 2015. Participants were given 10 mg ruxolitinib orally twice a day. Scores on the Brief Fatigue Inventory (BFI), CLL module of the MD Anderson Symptom Inventory (MDASI) and symptom-associated interference in daily activities, were assessed before treatment and after 3 months. This trial is ongoing and is registered at ClinicalTrials.gov (NCT02131584). FINDINGS: 41 patients (25 previously untreated for CLL and 16 previously treated) were enrolled. At 3 months, the mean percentage change from baseline in BFI score was 44·3% (SD 35·0, p<0·0001), in symptom interference score was 43·4% (51·5, p<0·0001), and in MDASI score was 42·1% (37·4, p<0·0001). 32 (78%) of the patients experienced 20% or greater reduction in the mean BFI, and 24 (59%) had a reduction of two units or more in worst fatigue score in past 24 hours as assessed by the BFI. The most comment grade 3-4 adverse events were neutropenia (n=2 [5%]), hypertension (n=2 [5%]), insomnia (n=1 [2%]), tinnitus and dizziness (n=1 [2%]), and thrombocytopenia (n=1 [2%]). INTERPRETATION: In patients with CLL, ruxolitinib was associated with significant improvements in disease-related symptoms as measured by BFI, MDASI, and symptom interference scores. Further studies to test the therapeutic efficacy of ruxolitinib in CLL are warranted. FUNDING: Incyte, National Cancer Institute.

The CXCR4-STAT3-IL-10 Pathway Controls the Immunoregulatory Function of Chronic Lymphocytic Leukemia and Is Modulated by Lenalidomide.

Chronic lymphocytic leukemia (CLL) cells possess regulatory functions comparable to those of normal B10 cells, a regulatory B cell subset that suppresses effector T-cell function through STAT3-mediated IL-10 production. However, the mechanisms governing IL-10 production by CLL cells are not fully understood. Here, we show that the CXC chemokine ligand 12 (CXCL12)-CXCR4-STAT3 axis regulates IL-10 production by CLL cells and their ability to suppress T-cell effector function through an IL-10 mediated mechanism. Knockdown of STAT3 significantly impaired the ability of CLL cells to produce IL-10. Furthermore, experiments to assess the role of lenalidomide, an immunomodulatory agent with direct antitumor effect as well as pleiotropic activity on the immune system, showed that this agent prevents a CXCL12-induced increase in p-S727-STAT3 and the IL-10 response by CLL cells. Lenalidomide also suppressed IL-10-induced Y705-STAT3 phosphorylation in healthy T cells, thus reversing CLL-induced T-cell dysfunction. We conclude that the capacity of CLL cells to produce IL-10 is mediated by the CXCL12-CXCR4-STAT3 pathway and likely contributes to immunodeficiency in patients. Lenalidomide appears to be able to reverse CLL-induced immunosuppression through including abrogation of the CXCL12-CXCR4-S727-STAT3-mediated IL-10 response by CLL cells and prevention of IL-10-induced phosphorylation of Y705-STAT3 in T cells.

Challenges and Successes in the Application of Universal Access Principles in the Development of Bus Rapid Transport Sytems in South Africa.

The National Department of Transport started a programme to upgrade public transport systems throughout South Africa in 2008, which included the upgrading of transport systems for host cities of the 2010 World Cup. This was the first time there was a clear commitment to produce universally accessible public transport systems in South Africa. The requirement to achieve universal access was reinforced by National Treasuries stipulation, that universal access was a precondition for the approval of all funding for these projects. In the absence of any specific legislation in the transport sector to address universal access and the South African National Building Regulations and the associated deemed to satisfy code, South African National Standard (SANS) 10400 Part S: "Facilities for Persons with Disabilities", providing the only associated standards, there has been a need to revisit traffic engineering codes. This has created an opportunity to look at the functionality and safety of commuters, especially those who have functional limitations, at traffic intersections and midblock pedestrian crossings, especially as the commuters have to access predominately median located Bus Rapid Transport (BRT) trunk stations. Included in the specific areas of focus that impact on the issues of pedestrian safety, has been the application and functionality of tactile wayfinding and warning surfaces and other support systems for commuters with functional sight limitations and the integration of the systems with other infrastructure and the safety of all commuter. In addition to the issues of functionality, this paper will address the influence of misdirected foreign expertise that set the initial BRT Systems on a high floor vehicle modality, which has created operational challenges that have seriously compromised functional universal access. This presentation will highlight these challenges, opportunities and solutions, the procedural complexities, as well as the inherent resistance by traffic engineers to new functional modalities, in the cites of Johannesburg, Cape Town, George, as well as the proposed BRT Systems in EThekwini and Ekurhuleni, through the paradigm of Universal Design.

Long-term durable remission by cladribine followed by rituximab in patients with hairy cell leukaemia: update of a phase II trial.

Nucleoside analogues are highly active in patients with hairy cell leukaemia (HCL); however, patients continue to relapse. This phase II study evaluated the efficacy and safety of cladribine followed by rituximab in patients with untreated HCL (N = 59), relapsed HCL (N = 14) and HCL variant (HCLv, N = 7). Cladribine 5·6 mg/m(2) was given intravenously (IV) daily for 5 d and was followed approximately 1 month later with rituximab 375 mg/m(2) IV weekly for 8 weeks. Complete response rate in patients with untreated HCL, relapsed HCL and HCLv was 100%, 100% and 86%, respectively. With a median follow up of 60 months, 5-year failure-free survival (FFS) in patients with untreated HCL, relapsed HCL and HCLv was 95%, 100% and 64%, respectively. Median duration of response to the cladribine followed by rituximab was significantly longer than the first-line cladribine single agent in patients who received this treatment as second-line treatment (72 months vs not reached, P = 0·004). Almost all patients (94%) achieved negative minimal residual disease (MRD) after the treatment. Positive MRD during the follow up did not necessarily result in clinically relevant relapse. Cladribine followed by rituximab is highly effective even in patients with relapsed disease and HCLv, and can achieve durable remission.

High fluorescence in situ hybridization percentage of deletion 11q in patients with chronic lymphocytic leukemia is an independent predictor of adverse outcome.

We have analyzed patients with previously untreated chronic lymphocytic leukemia with del11q fluorescence in situ hybridization (FISH) abnormality (n = 196) in this study. Detection of the 11q22.3 used a multicolor FISH technique. Patients with del11q fell into two major FISH subsets-sole del11q (n = 64) and del11q with del13q (n = 132). FISH subsets were compared using the median del11q FISH% (>58%, high vs. ≤58%, low). Overall survival (OS) and time to first treatment (TTFT) were estimated using Kaplan-Meier plots (log rank). Multivariate analysis was performed to assess the association between FISH% of del11q and outcomes. Patients with sole del11q were similar to del11q with del13q in terms of TTFT and OS. Patients with high FISH% of del11q had significantly shorter OS and TTFT as compared with patients with low FISH%, particularly in sole del11q; this negative impact of high FISH% of del11q on OS and TTFT was diminished with coexistent del13q. In multivariate analysis, high FISH% of del11q was a significant predictor for shorter OS and TTFT. A comparison of these del11q subsets with a separate cohort of (n = 673) previously untreated patients with sole del13q showed that the high FISH% del11q cohort had a significantly shorter TTFT and OS. In addition, bulky disease by physical examination or computed tomography imaging was infrequent at presentation in patients with del11q. High FISH% of del11q can reliably discriminate higher risk patients with chronic lymphocytic leukemia. Presence of coexistent del13q should be accounted for while prognosticating patients with del11q.

Probing the penetration of antimicrobial polymyxin lipopeptides into gram-negative bacteria.

The dry antibiotic development pipeline coupled with the emergence of multidrug resistant Gram-negative 'superbugs' has driven the revival of the polymyxin lipopeptide antibiotics. Polymyxin resistance implies a total lack of antibiotics for the treatment of life-threatening infections. The lack of molecular imaging probes that possess native polymyxin-like antibacterial activity is a barrier to understanding the resistance mechanisms and the development of a new generation of polymyxin lipopeptides. Here we report the regioselective modification of the polymyxin B core scaffold at the N-terminus with the dansyl fluorophore to generate an active probe that mimics polymyxin B pharmacologically. Time-lapse laser scanning confocal microscopy imaging of the penetration of probe (1) into Gram-negative bacterial cells revealed that the probe initially accumulates in the outer membrane and subsequently penetrates into the inner membrane and finally the cytoplasm. The implementation of this polymyxin-mimetic probe will advance the development of platforms for the discovery of novel polymyxin lipopeptides with efficacy against polymyxin-resistant strains.

Level of asthma control and health care utilization in Asia-Pacific countries.

BACKGROUND: Data on the impact of asthma in many countries in the Asia-Pacific region is limited. This study investigated whether partly- and uncontrolled asthma were associated with increased medication use/healthcare utilization and productivity loss among a population of asthma patients from nine Asia-Pacific countries. METHODS: We used cross-sectional data from 3630 asthma patients ≥12 years from the 2011 Asia-Pacific Asthma Insights and Management (AP-AIM) survey. Using Global Initiative for Asthma (GINA) guidelines, patients were categorized as having well-controlled, partly- controlled, or uncontrolled asthma. Chi-square tests were used to assess the relation of degree of asthma control with utilization of asthma medications, health services, productivity, and mood. RESULTS: Overall, 7.6% of the patients surveyed had asthma that was well-controlled, with the highest proportions in Singapore (14%) and the lowest in India (0%) and China (2%). Patients whose asthma was not well-controlled reported greater use of asthma medications, more emergency healthcare visits or hospitalizations for their asthma, and more interference of their mood due to asthma. They also reported significant decreases in productivity due to asthma. CONCLUSIONS: Patients who did not have well-controlled asthma had greater utilization rates of asthma medications and healthcare services and were more likely to report missing multiple days of work/school compared to patients whose asthma was well-controlled. These associations suggest that emphasis on improving asthma control could have dramatic effects on patient well-being and utilization of healthcare resources.

Thermal pretreatment of algae for anaerobic digestion.

The objective of this work was to determine the benefit of thermal pretreatment on biogas yield from microalgae-fed anaerobic digester mesocosms. Replicate Nanochloropsis oculata cultures were heated for 4h at 30, 60, and 90°C, as well as at a constant temperature of 90°C for 1, 3.5, and 12h. Net biogas production increased from 0.28L biogas/g volatile solids added (VSa) for the control to 0.39 L biogas/g VSa (p<0.01) when heated at 90°C, but there was no improvement at 30 or 60°C. Increased biogas production correlated with increased soluble chemical oxygen demand (COD). Net biogas production increased as a function of heating time, from 0.32 L biogas/g VSa for the control, to 0.41, 0.43, and 0.44 L biogas/g VSa (p<0.05 for all combinations vs. control) when preheated at 90°C for 1, 3.5, and 12h, respectively. However, despite enhanced biogas production the energy balance is negative for thermal pretreatment.

Avoiding digester upset.

The acetate uptake bioassay (AUB) is a predictive measure for determining the stability of anaerobic digesters, but its use is rare due to the limited availability of gas chromatography equipment at wastewater treatment facilities. A water displacement system was compared and evaluated as an alternative to gas chromatography analysis for conducting the AUB. Results indicated that methane generation rates measured by the two methods were statistically the same. Precision of the method varied by less than 5%. Accuracy was quantified by measuring near stoichiometric volumes of carbon dioxide gas production from abiotic tests using sodium carbonate and hydrochloric acid. The method detection limit (MDL) was 0.6 mL. The effective use of a water displacement system as a surrogate for gas chromatography analysis could make the adoption of the AUB for predicting digester stability a practical option for treatment facilities.